A Common Fold Mediates Vertebrate Defense and Bacterial Attack Academic Article uri icon

abstract

  • Proteins containing membrane attack complex/perforin (MACPF) domains play important roles in vertebrate immunity, embryonic development, and neural-cell migration. In vertebrates, the ninth component of complement and perforin form oligomeric pores that lyse bacteria and kill virus-infected cells, respectively. However, the mechanism of MACPF function is unknown. We determined the crystal structure of a bacterial MACPF protein, Plu-MACPF from Photorhabdus luminescens, to 2.0 angstrom resolution. The MACPF domain reveals structural similarity with poreforming cholesterol-dependent cytolysins (CDCs) from Gram-positive bacteria. This suggests that lytic MACPF proteins may use a CDC-like mechanism to form pores and disrupt cell membranes. Sequence similarity between bacterial and vertebrate MACPF domains suggests that the fold of the CDCs, a family of proteins important for bacterial pathogenesis, is probably used by vertebrates for defense against infection.

authors

  • Rosado, CJ
  • Buckle, AM
  • Law, RHP
  • Butcher, RE
  • Kan, W-T
  • Bird, CH
  • Ung, K
  • Browne, KA
  • Baran, K
  • Bashtannyk-Puhalovich, TA
  • Faux, NG
  • Wong, W
  • Porter, CJ
  • Pike, RN
  • Ellisdon, AM
  • Pearce, MC
  • Bottomley, SP
  • Emsley, J
  • Smith, AI
  • Rossjohn, J
  • Hartland, EL
  • Voskoboinik, I
  • Trapani, JA
  • Bird, PI
  • Dunstone, MA
  • Whisstock, JC

publication date

  • September 14, 2007

has subject area